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MedNess: bite-size biopharma and medtech news

3rd February, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Amgen’s Sotorasib demonstrated clinical meaningful results in previously treated KRAS+ NSCLC
On 28th January, Amgen announced that its KRASG12C inhibitor, Sotorasib (AMG 510), demonstrated durable, meaningful results from the KRASG12C+ NSCLC cohort of the registrational Phase II CodeBreaK 100 trial.
Background: KRAS has remained a difficult therapeutic target for many decades and tumors harbouring KRAS mutations are associated with poor prognosis. Apart from efficacy, targeting KRAS also involves considerable safety issues. KRASG12C mutations are present in ~14% of NSCLC adenocarcinoma, 3-4% of CRC and in subsets of various other tumors. Additionally, ~25,000 and ~33,000 patients are diagnosed with KRASG12C-mutated NSCLC each year in the US and EU-27, respectively.
Earlier, in December Sotorasib was granted the Breakthrough Therapy Designation by the US FDA and is also under regulatory review by the agency under its Real-Time Oncology Review (RTOR) pilot program. Amgen has also submitted the Marketing Authorization Application (MAA) for Sotorasib to the European Medicines Agency (EMA). Just last week, Sotorasib was also granted Breakthrough Therapy Designation in China.
Details: Sotorasib was being evaluated in 126 previously treated, KRASG12C+ NSCLC patients. At a median follow-up of 12.2 months (data cut-off – 1st Dec. 2020), it demonstrated an ORR and DCR of 37.1% (3CR, 43PR) and 80.6%, respectively. The median best tumor shrinkage amongst responders was 60%. The median DoR and PFS were 10.0 and 6.8 months, respectively while the median time to response was 1.4 months.
Sotorasib was well tolerated with mostly grade 1-2 TRAEs, no treatment-related deaths and only 7.1% patients discontinuing treatment due to TRAEs. Grade 3/4 TRAEs were reported in 19.8%/0.8% patients. These results were consistent with the data from Phase I study in previously treated NSCLC patients with KRAS G12C-mutation.
81% patients in the NSCLC cohort had progressed on both platinum-based chemotherapy and PD1/L1 inhibitors, while remaining patients had progressed on one of these treatments.
Implications: Sotorasib is the first KRASG12Ci to demonstrate PFS in this patient population and until now patients with KRASG12C mutation with progressive disease had limited treatment options. Amgen cracked the code for drugging KRAS and expects to launch the drug in Q3 in the US, once approved.
Sotorasib is also being evaluated in several combinations across different tumors for enhanced efficacy. Amgen initiated a randomized Phase III CodeBreak 200 study for Sotorasib in KRASG12C+ NSCLC. Addiitonally, the once-daily oral formulation of Sotorasib offers several advantages as compared to intravenous infusions. Mirati/BI which announced a collaboration in September 2020 for KRAS-driven cancers remain close competitors for Amgen.

Collated by : Shilpa Rawal, PhD
Drug Approvals
European Commission Approves KEYTRUDA® (pembrolizumab) in 1L MSI-H or dMMR CRC patients
“Before the KEYNOTE-177 trial, conventional chemotherapy with targeted therapy was the standard of care for patients with metastatic colorectal cancer who have tumors that are MSI-H/dMMR,” said Dr. Thierry Andre, professor of medical oncology at Sorbonne University and head of the medical oncology department at St. Antoine Hospital, Assistance Publique Hôpitaux de Paris. “With this approval, patients with metastatic colorectal cancer that is MSI-H or dMMR status will gain a monotherapy treatment option that has shown superior progression-free survival compared to standard of care chemotherapy.”
Calquence approved in Japan for the treatment of R/R CLL
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “Chronic lymphocytic leukaemia is less prevalent in Japan than other regions, yet patients remain in need of innovative treatment options. This approval of Calquence offers patients in Japan a new, chemo-free, tolerable treatment option with uncompromised efficacy and the potential to positively impact quality of life.”
 
Regulatory News
FDA Clearance of IND for TNB-585 and Initiation of Ph I trial for mCRPC Announced
Suhasini Iyer, CDO of Teneobio said, “As shown at the recent American Society of Hematology meeting (2020), the phase I data on TNB-383B, our anti-BCMAxCD3 bispecific, validated our hypothesis that uncoupling cytotoxicity from cytokine release was clinically feasible in treating multiple myeloma. We are excited to bring this unique CD3 redirecting platform profile to bear on mCRPC via TNB-585. An improved safety profile in T-cell redirection for mCRPC may enable future more efficacious combination treatments with standard-of-care therapies. Moreover, TNB-585 has a predicted half-life of over two weeks that enables a patient- and provider-focused dosing schedule.”
 
“I am pleased that our team was able to address the FDA’s clinical hold questions in a timely manner, enabling us to evaluate BPX-601 in a cohort of patients with previously treated metastatic prostate cancer,” said Rick Fair, President and CEO of Bellicum Pharmaceuticals. “I remain optimistic about the safety and potential clinical benefit of our BPX-601 product candidate in these patients.”
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Trial Results
“We are excited to announce the improved overall survival observed in another Phase 3 trial for tislelizumab when compared to chemotherapy standard of care. This is our fourth positive Phase 3 readout for tislelizumab and the first from our large Phase 3 program in gastrointestinal cancers that also include liver, stomach cancers as well as esophageal cancer,” commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. “With our ongoing evaluation of tislelizumab across multiple tumor types, we are working to provide clinical evidence and bring this potentially differentiated anti-PD-1 antibody to far more patients around the world.”
New investigational data on LENVIMA to be presented at GU21 meeting
"We're excited to present new investigational data on LENVIMA that we hope will provide the oncology community with optimism at this year's Genitourinary Cancers Symposium," said Dr. Takashi Owa, Vice President, Chief Medicine Creation Officer and Chief Discovery Officer, Oncology Business Group at Eisai. "We remain relentless in our pursuit to spark change in the oncology space by continuing to evaluate the LENVIMA plus everolimus combination as well as research new potential combination treatment options for renal cell carcinoma patients. We're dedicated to fighting for patients suffering from this insidious disease and we believe these results mark a big step in the direction of greater therapeutic knowledge and options for this community."
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Trial/Program Status
Positive Results Presented for Mobocertinib in Patients with EGFR Exon20 Insertion+ mNSCLC who Received Prior Platinum-Based Chemotherapy
“Results show mobocertinib demonstrated clinically meaningful responses and a noteworthy duration of response in patients with EGFR Exon20 insertion+ mNSCLC who received prior platinum-based therapy,” said Pasi A. Jänne, M.D., Ph.D., Dana-Farber Cancer Institute. “These data are promising and provide further evidence for mobocertinib as a potential oral treatment for patients with EGFR Exon20 insertion+ mNSCLC, who are in critical need of targeted treatment options.”
HER2 Bispecific Antibody-Drug Conjugate, ZW49, Advanced into Expansion Cohort Stage of Clinical Development
“We are encouraged by the antitumor activity we are seeing so far with ZW49 and look forward to accelerating development by expanding our dataset in disease-specific cohorts,” said Diana Hausman, M.D., Chief Medical Officer of Zymeworks. “In addition, the differentiated safety profile allows us to continue in dose escalation, with the opportunity to fully realize the therapeutic potential for ZW49.”
Click here for more Trial Statuses
Medness Business
Onco-News
Nuvalent Launches with $50M Series A Financing from Deerfield Management to Develop Precisely Targeted Kinase Inhibitors for Treatment-Resistant Cancers
“Kinase inhibitors remain at the leading edge of targeted therapies for patients with cancer, but the clinical utility of currently available treatments is limited by resistance mutations and off-target effects,” said Dr. Porter. “At Nuvalent, we are leveraging our expertise in structure-based design to solve for the dual challenges of resistance and selectivity, with the goal of driving deeper and more durable responses for patients living with cancer. We have partnered with leading physician-scientists to understand the limitations of existing cancer therapies that target proven oncogenic kinases and assembled an accomplished team to translate those insights into a novel pipeline of precisely targeted therapies.”
Tempus Expands Licensing Agreement with Bristol Myers Squibb to Analyze and Discover RNA-Based Targets
“With Tempus’ whole-transcriptome sequencing datasets, it’s now possible to analyze known and novel RNA expression targets connected to real-world treatments and outcomes,” said Ryan Fukushima, Chief Operating Officer of Tempus. “Our work with Bristol Myers Squibb has made it possible to transform terabytes of data into clinically relevant insight by stratifying diseases into key molecular subtypes and uncovering potentially better ways to treat patients going forward.”
Click here for more on mergers, acquisition and business news
Collated by : Richa Tewari, PhD
Editors' Desk
Richa Tewari, PhD
Oncology News
Esha Sehanobish, PhD
MedNess Plus
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Shilpa Rawal, PhD
Onco I-Analyse
Debarati Banik
HealthIT
Rinki Saha
BioPharma News
Abhi Dey
Consulting Editor
Nisha Peter, PhD
Managing Editor
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The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Medness. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Medness. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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Content Editors: Richa Tewari , Esha Sehanobish , Rinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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